Summary
β‐thalassaemia is one of the commonest autosomal recessive single‐gene disorders worldwide. Prenatal tests use invasive methods, posing a risk for the pregnancy itself. Development of a ...noninvasive prenatal diagnostic method is, therefore, of paramount importance. The aim of the present study is to identify high‐heterozygote informative single‐nucleotide polymorphisms (SNPs), suitable for the development of noninvasive prenatal diagnosis (NIPD) of β‐thalassaemia. SNP genotyping analysis was performed on 75 random samples from the Cypriot population for 140 SNPs across the β‐globin cluster. Shortlisted, highly heterozygous SNPs were then examined in 101 carrier families for their applicability in the noninvasive detection of paternally inherited alleles. Forty‐nine SNPs displayed more than 6% heterozygosity and were selected for NIPD analysis, revealing 72.28% of the carrier families eligible for qualitative SNP‐based NIPD, and 92% for quantitative detection. Moreover, inference of haplotypes showed predominant haplotypes and many subhaplotypes with sufficient prevalence for diagnostic exploitation. SNP‐based analyses are sensitive and specific for the detection of the paternally inherited allele in maternal plasma. This study provides proof of concept for this approach, highlighting its superiority to NIPD based on single markers and thus providing a blueprint for the general development of noninvasive prenatal diagnostic assays for β‐thalassaemia.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Summary beta-thalassaemia is one of the commonest autosomal recessive single-gene disorders worldwide. Prenatal tests use invasive methods, posing a risk for the pregnancy itself. Development of a ...noninvasive prenatal diagnostic method is, therefore, of paramount importance. The aim of the present study is to identify high-heterozygote informative single-nucleotide polymorphisms (SNPs), suitable for the development of noninvasive prenatal diagnosis (NIPD) of beta-thalassaemia. SNP genotyping analysis was performed on 75 random samples from the Cypriot population for 140 SNPs across the beta-globin cluster. Shortlisted, highly heterozygous SNPs were then examined in 101 carrier families for their applicability in the noninvasive detection of paternally inherited alleles. Forty-nine SNPs displayed more than 6% heterozygosity and were selected for NIPD analysis, revealing 72.28% of the carrier families eligible for qualitative SNP-based NIPD, and 92% for quantitative detection. Moreover, inference of haplotypes showed predominant haplotypes and many subhaplotypes with sufficient prevalence for diagnostic exploitation. SNP-based analyses are sensitive and specific for the detection of the paternally inherited allele in maternal plasma. This study provides proof of concept for this approach, highlighting its superiority to NIPD based on single markers and thus providing a blueprint for the general development of noninvasive prenatal diagnostic assays for beta-thalassaemia. PUBLICATION ABSTRACT
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Abstract Classic Rett Syndrome (RS) is a neurodevelopmental disorder due to mutations in the MECP2 gene in Xq28. Atypical RS with severe early-onset encephalopathy and therapy-resistant epilepsy can ...be due to mutations in the CDKL5 (Cyclin-Dependent Kinase-like 5) gene in Xp22. We here report a 14-year-old female with a RS-like clinical picture, and well-controlled seizures. MECP2 gene testing was negative, but subsequent sequencing of the CDKL5 gene revealed the c. 2908 C > T nonsense mutation (p.Arg970X) in the last exon, not previously described in other patients or controls. The less severe phenotype might be due to the position of the mutation in the last exon of the CDKL5 gene.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background: Injuries represent an important public health problem but their incidence is difficult to estimate. Methods: We conducted a population-based household survey in Greece covering 4079 ...interviewed individuals. The interviewees reported, for themselves and for cohabitating adults (age 15 years and older; n = 7157), injuries that occurred during the preceding year. Major injuries were defined as those requiring contact with a health institution. We compared these survey data with data obtained through a national Emergency Department Injury Surveillance System (EDISS). Results: For the month closest to the survey interview, the incidence reported for the responders was 5.9 per 100 person-year, whereas the incidence for cohabitating adults was 3.7 per 100 person-years. These incidence rates declined for months more remote to the interview. Comparison of survey and EDISS data suggested that survey reporting was less accurate for nontraffic-related injuries. Taking into account possible recall and telescoping biases, the best survey estimate of the national annual number of major injuries is 525,000 (5.9 per 100 person-year), whereas the EDISS data yielded an estimate of 1,150,000 major injuries (12.9 per 100 person-years) Conclusions: Comparison of survey and EDISS data systems provides quantitative assessment of accuracy of the survey data in relation to time of injury before report date, to severity of injury, and to whether the injury is to the interviewee or to a cohabitant. The 2 systems could be used in a complementary way, although EDISS generates information that is medically more accurate and is a more cost-effective data collection system.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
